Recurrent cytokine release syndrome in patients receiving bispecific antibody therapy for multiple myeloma: a case series

: Bispecific antibodies targeting B-cell maturation antigen, BCMA (teclistamab) or G protein–coupled receptor, class C, group 5 member D, GPRC5D (talquetamab) are effective treatments for relapsed or refractory multiple myeloma. Their main early toxicity is cytokine release syndrome (CRS), usually transient and limited to initial cycles. We report five patients with relapsed or refractory multiple myeloma who received bispecific antibodies (n = 1 teclistamab; n = 4 talquetamab) who developed a pattern of recurrent, cyclic CRS beyond the initial step-up phase. All patients achieved at least a partial hematologic response, with complete or stringent complete remission in most cases. Recurrent febrile episodes occurred at regular intervals after drug administration, despite repeatedly negative infectious workups. CRS episodes were generally grade 1–2 and resolved with tocilizumab, with or without corticosteroids. In one patient treated with teclistamab, recurrent CRS contributed to treatment discontinuation due to renal complications. Attenuation of CRS severity over time was observed in some patients, allowing treatment continuation with tailored premedication strategies. This case series describes an unusual pattern of recurrent CRS occurring during bispecific antibody therapy for multiple myeloma. Recognition of this phenomenon is essential to avoid misdiagnosis as infection and unnecessary antimicrobial use. Systematic reporting of such real-world adverse events may help refine supportive care strategies.